LAUSR

BACKGROUND Gentamicin is used to treat severe infections and has a small therapeutic window. This study aimed to optimize the dosing strategy of gentamicin in intermittently hemodialyzed patients by simulating concentration/time profiles during pre- and post-dialysis dosing, based on a published pharmacokinetic model. METHODS Pharmacokinetic simulations were performed with virtual patients, including septic patients, who were treated with gentamicin and received weekly hemodialysis with an interval of 48h-48h-72h. The following dosing regimens were simulated: for non-septic patients, 5 mg/kg gentamicin was given 1h/2h before dialysis, or a starting dose of 2.5 mg/kg and a maintenance dose of 1.5 mg/kg immediately after dialysis; for septic patients, 6 mg/kg gentamicin was given 1h/2h before dialysis, or a starting dose of 3 mg/kg and a maintenance dose of 1.8 mg/kg immediately after dialysis. The mean Cmax, AUC24h, and target attainment (TA) of pharmacodynamic targets were calculated and compared. The following targets were adopted from literature: Cmax >8 mg/L and <20 mg/L and AUC24h >70 mg·h/L and <120 mg·h/L. RESULTS In non-septic patients, postdialysis dosing resulted in a TA of 35% for Cmax >8 mg/L, 100% for <20 mg/L and AUC24h >70 mg·h/L, and 45% for <120 mg·h/L. Dosing 2h prior to dialysis resulted in a TA of 100% for Cmax> 8 mg/L, 40% for <20 mg/L, 65% for AUC24h >70 mg·h/L, and 77% for <120 mg·h/L. Simulations of septic patients resulted in comparable outcomes with higher TAs for Cmax <20 mg/L (96%), AUC24h >70 mg·h/L (90%), and <120 mg·h/L (53%) for dosing 1h prior to dialysis. CONCLUSIONS Postdialysis dosing resulted in a low TA of Cmax >8 mg/L; however, predialysis dosing ensured a high TA of Cmax >8 mg/L and acceptable TA of Cmax <20 mg/L, AUC24h >70 mg·h/L, and <120 mg·h/L, which could increase the efficacy of gentamicin. Therefore, clinicians should consider predialysis dosing of gentamicin in patients undergoing intermittent hemodialysis.